Autoimmune disorders develop as a result of deregulated immune responses that target self-antigens and cause destruction of healthy host tissues. Because dendritic cells (DCs) play an important role in the maintenance of peripheral immune tolerance, we are interested in identifying means of enhancing their therapeutic potential in autoimmune diseases. It is thought that during steady state, DCs are able to anergize potentially harmful T cells bearing T cell receptors that recognize selfpeptide-major histocompatibility complexes. The tolerogenic capacity of DCs requires an immature phenotype, which is characterized by a reduced expression of costimulatory molecules. On the contrary, activation of antigen-specific naive T cells is enhanced by DC maturation, a process that involves expression of genes controlled by the transcription factor nuclear factor (NF)-B. We evaluated the capacity of drugs that inhibit NF-B to enhance the tolerogenic properties of immature DCs in the experimental autoimmune encephalomyelitis (EAE) model. We show that andrographolide, a bicyclic diterpenoid lactone, and rosiglitazone, a peroxisome proliferatoractivated receptor ␥ agonist, were able to interfere with NF-B activation in murine DCs. As a result, treated DCs showed impaired maturation and a reduced capacity to activate antigen-specific T cells. Furthermore, NF-B-blocked DCs had an enhanced tolerogenic capacity and were able to prevent EAE development in mice. The tolerogenic feature was specific for myelin antigens and involved the expansion of regulatory T cells. These data suggest that NF-B blockade is a potential pharmacological approach that can be used to enhance the tolerogenic ability of immature DCs to prevent detrimental autoimmune responses.

PPARγ is a ligand-activated nuclear receptor best known for its involvement in adipogenesis and glucose homeostasis. PPARγ activity has also been associated with neuroprotection in different neurological disorders, but the mechanisms involved in PPARγ effects in the nervous system are still unknown. Here we describe a new functional role for PPARγ in neuronal responses to injury. We found both PPAR transcripts and protein within sensory axons and observed an increase in PPARγ protein levels after sciatic nerve crush. This was correlated with increased retrograde transport of PPARγ after injury, increased association of PPARγ with the molecular motor dynein, and increased nuclear accumulation of PPARγ in cell bodies of sensory neurons. Furthermore, PPARγ antagonists attenuated the response of sensory neurons to sciatic nerve injury, and inhibited axonal growth of both sensory and cortical neurons in culture. Thus, axonal PPARγ is involved in neuronal injury responses required for axonal regeneration. Since PPARγ is a major molecular target of the thiazolidinedione (TZD) class of drugs used in the treatment of type II diabetes, several pharmaceutical agents with acceptable safety profiles in humans are available. Our findings provide motivation and rationale for the evaluation of such agents for efficacy in central and peripheral nerve injuries.

Autoimmunity develops when the adaptive immune system reacts against self-antigens, causing destruction or altered function of the host’s own healthy tissues. Although the mechanisms responsible for the loss of tolerance to self have not yet been fully elucidated, it is thought that both genetic predisposition and environmental triggers may be involved. Considering that dendritic cells (DCs) are the antigen- presenting cells (APCs) determining the primary activation of naïve T cells, they play a pivotal role in the regulation of adaptive immunity and the maintenance of immune tolerance to self-antigens. It is thought that T cells recognizing self-constituents in the periphery are kept under control by immature DCs, through the presentation of self-antigens in the absence of costimulation. Thus, alterations in the physiology of DCs could be responsible for incomplete tolerance to self. The main focus of this review will be the capacity of the immunological synapse occurring at the DC/T-cell interface to fine-tune the balance between tolerance and immunity and how alterations on some of the constituents that participate in the synapse can determine induction or perpetuation of undesired immune responses. Factors modulating DC function and thus influencing the course of the adaptive immunity, such as activating/inhibitory receptors expressed on the surface of DCs, and pharmacological approaches will be also discussed.

Se presenta un caso clínico, en el cual el paciente es masculino, de edad avanzada, con diversas patologías, quien por cuestiones religiosas no acepta transfusiones, por lo que se le ofrecen tratamientos alternativos.

Son un tipo de lesiones a nivel genital, ásperas y duras con un aspecto de coliflor, suelen estar acompañados de hidrocele más una masa paratesticular o epididimaria.